Short communication Zinc treatment induces cortical brain-derived neurotrophic factor gene expression Gabriel Nowak a,b, * , Beata Legutko a , Bernadeta Szewczyk a , Mariusz Papp a , Marek Sanak a , Andrzej Pilc a,c a Institute of Pharmacology, Polish Academy of Sciences, Sme ßtna 12, PL 31-343, Cracow, Poland b Department of Pharmacobiology, Collegium Medicum, Jagiellonian University, Cracow, Poland c Institute of Public Health, Collegium Medicum, Jagiellonian University, Cracow, Poland Received 12 March 2004; accepted 23 March 2004 Available online 26 April 2004 Abstract Most of antidepressants induce expression of the gene coding for brain-derived neurotrophic factor (BDNF) in the hippocampal/cortical neurons. Recent data indicate antidepressant-like activity of zinc in animal models. We now report that chronic treatment with zinc induced an increase in cortical but not hippocampal BDNF mRNA level (Northern blot). Tranylcypromine, a classic antidepressant, increased BDNF mRNA level in both examined brain regions. This is the first demonstration that zinc increases the BDNF gene expression, which is the effect shared by most of clinically effective antidepressants. D 2004 Elsevier B.V. All rights reserved. Keywords: Zinc; BDNF; Cortex; Hippocampus 1. Introduction Zinc is an endogenous neuromodulator of glutamate (mainly N-methyl-D-aspartatic acid—NMDA) receptors which may be involved in the psychopathology and treatment of depression (Nowak and Szewczyk, 2002). Zinc exhibits antidepressant-like effects in the forced swim and tail sus- pension tests and is also active in olfactory bulbectomy and chronic mild stress animal models of depression (Kroczka et al., 2001; Nowak et al., 2003b; Rosa et al., 2003, our unpublished data). All these data strongly suggest possible antidepressant activity of zinc in human depression. In fact, our preliminary clinical study demonstrated beneficial effect of zinc supplementation in antidepressant therapy (Nowak et al., 2003a). According to the recently proposed hypotheses, the brain- derived neurotrophic factor (BDNF) is involved in the mechanism of antidepressant action as one of the main targets of antidepressants (Nibuya et al., 1995). Antidepressant drugs or electroconvulsive therapy in- duced an increase in hippocampal (and cortical) BDNF mRNA level (Nibuya et al., 1995). Although there are some discrepancies in antidepressant dosing and treatment sched- ules, which are appropriate for affecting BDNF, undoubt- edly, antidepressants influence BDNF gene expression (Nibuya et al., 1995; Coppel et al., 2003). Since most effects of antidepressants on BDNF gene expression were demonstrated after prolonged treatment, in the present study we investigated the effect of chronic (2- week) treatment with zinc on BDNF mRNA level in the rat cerebral cortex and hippocampus. In order to control exper- imental conditions, we also determined the effect of a classic antidepressant drug, an inhibitor of monoamine oxidase, tranylcypromine. 2. Materials and methods 2.1. Animals All procedures were conducted according to the guide- lines of the National Institutes of Health Animal Care and Use Committee, and were approved by the Ethics Com- 0014-2999/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2004.03.038 * Corresponding author. Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Sme ßtna 12, PL 31-343, Cracow, Poland. Tel.: +48-12-6623215; fax: +48-12-637-4500. E-mail address: nowak@if-pan.krakow.pl (G. Nowak). www.elsevier.com/locate/ejphar European Journal of Pharmacology 492 (2004) 57 – 59